Background Anti-MDA5 antibody is one of dermatomyositis-specific autoantibodies and its characteristic clinical meanings have been reported. It associates with clinically amyopathic dermatomyositis (CADM), hyperferritinemia, acute or subacute interstitial pneumonia (A/SIP) and poor prognosis especially in Asian patients. Recently, an ELISA system which can detect anti-MDA5 antibody was established and some reported that its titer seems to be associated with disease activity. However, it has not been yet clear how anti-MDA5 titer changes during long term or whether it associates with other clinical markers.
Objectives We followed anti-MDA5 titer closely and longitudinal clinical course.
Methods We prepared recombinant His-MDA5 protein (520a.a. of c-terminus) expressed in Eschericha coli. After confirming antigenic activity of the recombinant protein using immunoblotting, we made an ELISA system. Efficiency was confirmed using the sera from 31 Japanese DM patients (23 anti-MDA5-positive and 8 anti-MDA5 negative patients) and 25 healthy controls. The presence of Anti-MDA5 was confirmed by immunoprecipitation using 35S-methionine-labeled HeLa cells. Sera from 14 anti-MDA5-positive patients were collected during disease course (range: 3-133 weeks). The titer at 0, 4, 8, 12 weeks of the disease course were compared. The association between the titer and several serum markers (ferritin, KL-6, IL-6 and M-CSF) were assessed.
Results The cut-off point was defined at 56.7 U on the basis of mean+4SD of healthy controls and both sensitivity and specificity of the ELISA were 100%. In anti-MDA5-positive patients, the antibody titer tended to be higher in the deceased (n=7) than in the alive (n=11) but there was no statistical significance (p=0.057). In the alive patients, the anti-MDA5 titer gradually decreased especially 8 weeks after the desease onset. After 11 weeks, the antibody titer decreased under the cut-off point in some patients and after 52 weeks, the titer went down to the mean level of the healthy control in 4 of 5 patients. There was no association between anti-MDA5 titer and serum ferritin or IL-6 levels before treatment but anti-MDA5 titer was correlated with serum ferritin in 3 of 6 patients at longitudinal study in each disease course. In one patient, KL-6 was also associated with the antibody titer. IL-6 and M-CSF were not associated with the titer during the disease course.
Conclusions The ELISA system for anti-MDA5 antibody is useful not only in diagnosis of DM but also in estimating prognosis and following disease activity during longitudinal time course in each patients.
References Sato S, et al. Mod Rheumatol 2012 May 29 [ahead of print]
Gono T, et al. Rheumatology (Oxford). 2012 Sep;51(9):1563-70.
Disclosure of Interest None Declared